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dc.contributor.authorAndlauer, Till F M
dc.contributor.authorGuzman-Parra, Jose
dc.contributor.authorStreit, Fabian
dc.contributor.authorStrohmaier, Jana
dc.contributor.authorGonzález, Maria José
dc.contributor.authorGil Flores, Susana
dc.contributor.authorCabaleiro Fabeiro, Francisco J
dc.contributor.authorDel Río Noriega, Francisco
dc.contributor.authorPerez, Fermin Perez
dc.contributor.authorHaro González, Jesus
dc.contributor.authorOrozco Diaz, Guillermo
dc.contributor.authorde Diego-Otero, Yolanda
dc.contributor.authorMoreno-Küstner, Berta
dc.contributor.authorAuburger, Georg
dc.contributor.authorDegenhardt, Franziska
dc.contributor.authorHeilmann-Heimbach, Stefanie
dc.contributor.authorHerms, Stefan
dc.contributor.authorHoffmann, Per
dc.contributor.authorFrank, Josef
dc.contributor.authorFoo, Jerome C
dc.contributor.authorTreutlein, Jens
dc.contributor.authorWitt, Stephanie H
dc.contributor.authorCichon, Sven
dc.contributor.authorKogevinas, Manolis
dc.contributor.authorRivas, Fabio
dc.contributor.authorMayoral, Fermín
dc.contributor.authorMüller-Myhsok, Bertram
dc.contributor.authorForstner, Andreas J
dc.contributor.authorNöthen, Markus M
dc.contributor.authorRietschel, Marcella
dc.date.accessioned2023-02-13T20:30:42Z
dc.date.available2023-02-13T20:30:42Z
dc.date.issued2019-11-11
dc.identifier.citationAndlauer TFM, Guzman-Parra J, Streit F, Strohmaier J, González MJ, Gil Flores S, Cabaleiro Fabeiro FJ, Del Río Noriega F, Perez FP, Haro González J, Orozco Diaz G, de Diego-Otero Y, Moreno-Küstner B, Auburger G, Degenhardt F, Heilmann-Heimbach S, Herms S, Hoffmann P, Frank J, Foo JC, Treutlein J, Witt SH, Cichon S, Kogevinas M; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Rivas F, Mayoral F, Müller-Myhsok B, Forstner AJ, Nöthen MM, Rietschel M. Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. Mol Psychiatry. 2021 Apr;26(4):1286-1298. doi: 10.1038/s41380-019-0558-2. Epub 2019 Nov 11. PMID: 31712721; PMCID: PMC7985020.en_US
dc.identifier.eissn1476-5578
dc.identifier.doi10.1038/s41380-019-0558-2
dc.identifier.pmid31712721
dc.identifier.urihttp://hdl.handle.net/20.500.12648/8360
dc.description.abstractMultiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
dc.language.isoenen_US
dc.relation.urlhttps://www.nature.com/articles/s41380-019-0558-2en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleBipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleMolecular psychiatryen_US
dc.source.volume26
dc.source.issue4
dc.source.beginpage1286
dc.source.endpage1298
dc.source.countryUnited Kingdom
dc.source.countryUnited Kingdom
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.description.versionVoRen_US
refterms.dateFOA2023-02-13T20:30:42Z
html.description.abstractMultiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
dc.description.institutionSUNY Downstateen_US
dc.description.departmentPsychiatry and Behavioral Sciencesen_US
dc.description.departmentInstitute for Genomics in Healthen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalMolecular psychiatry


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